Role of Protein Corona in the Fate of Hydrophilic Polymeric Nanoparticles: A Fundamental Study

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Nanoparticles are particles of matter with dimensions on the order of nanometers. In a biological environment, nanoparticles acquire a layer of proteins, called a corona, and the composition of their corona critically affects the biological fate of nanoparticles. Although a variety of studies have been done to understand the protein corona of nanoparticles over the past decade, little is known about protein corona formed on commonly used hydrophilic (i.e., "water loving") biopolymer nanoparticles. The research team on this project will study the protein corona formed against a number of hydrophilic biopolymers. The objectives are to decode the compositions of the protein coronas and to correlate the identified proteins with the surface chemistry of the nanoparticles. The researchers will then use this knowledge to further understand the biological fate of the nanoparticles. This research will enhance our fundamental understanding of protein corona, identify key proteins responsible for the promotion or reduction of cellular uptake, and guide the design of better and safer nanoparticles for a broad range of applications. The research project serves as a training ground for graduate and undergraduate students to perform cutting edge research. The research team will recruit undergraduate students, particularly students underrepresented in STEM fields, through various on-campus programs. Knowledge from this work will be disseminated through presentations at international conferences, the development of curricula for new courses, and outreach activities. Protein corona on nanoparticles have been shown to be determinant for the biological fate of nanoparticles. At present, most research has focused on corona formation on model hydrophobic polystyrene or inorganic nanoparticle systems. Little is known about protein corona formed on the most commonly used hydrophilic biopolymer nanoparticles. The objectives of this study are to decode the compositions of protein coronas formed against a number of hydrophilic biopolymers using a well-defined, hydrogel nanoparticle system and to correlate the identified proteins with the surface chemistry and fate of nanoparticles. Magnetic nanoparticles will be encapsulated inside the hydrogel nanoparticles to enable the facile harvesting of protein corona using a magnetic field. The compositions of protein coronas will be decoded using state-of-the-art proteomic analysis to provide insights into the interaction of plasma proteins with these hydrophilic polymers. The impact of these adsorbed proteins on the fate of the nanoparticles will be investigated further through cellular uptake experiments using both macrophage and dendritic cells. A fundamental understanding of protein corona will guide the design of better and safer nanoparticles for a wide range of biomedical and engineering applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.